“Pathogens manipulate the host immune response to favor their own survival or exploit inherent weaknesses in the immune system.”

Michael Russell, PhD, Professor

Dept. of Microbiology and Immunology

BUFFALO, N.Y. — With drug resistance on the rise and the
emergence of increasingly deadly viral pathogens, scientists must
develop a better understanding of the human immune system and its
adaptability in order to take full advantage of it, writes a
University at Buffalo immunologist.

“It is…time to think of and exploit new ways of
dealing with the age-old problem of infectious disease,”
writes Michael W. Russell, PhD, professor in the Department of
Microbiology and Immunology in the University at Buffalo School of
Medicine and Biomedical Sciences. His opinion piece was published
today in the journal mBio.

Fewer drugs are effective against some viruses and eukaryotic
pathogens due to resistance, he writes, “most notably in the
case of malaria, where resistance to artemisinin appeared sooner
than anticipated.” That’s why, he writes, science
should no longer view microbial pathogenicity “as a simple
linear process” between the pathogen, which attacks, and the
host, which defends.

Instead, he says, complex and ingenious responses occur as the
pathogen reacts to the host and the host to the pathogen. By better
understanding the methods that pathogens use to constantly stay one
step ahead of immune defenses, scientists can learn to
“counter-manipulate” how pathogens subvert the immune
response, thereby inducing effective immunity.

“Pathogens manipulate the host immune response to favor
their own survival or exploit inherent weaknesses in the immune
system,” he explains. To get around the problem of
resistance, he suggests directly targeting the immune system.
“We can do this by tweaking it in some way to generate
effective immune responses, avoiding the problem of antibiotic
resistance, which threatens to render some infections untreatable,
amid the emergence of so-called ‘superbugs,’” he
says.

Recent research has revealed that both pathogen and host have
sensory mechanisms that quickly detect the presence of the other so
that, he writes, “…the outcome may be an emergent
property of the interaction between host and pathogen, not easily
predictable from separate consideration of their
characteristics.”

Russell’s understanding of these intricate interactions
comes from his research on the pathogen that causes gonorrhea,
recently cited by the Centers for Disease Control as one of the top
three pathogens requiring urgent action. The World Health
Organization has warned of a pending gonorrhea crisis due to
soaring drug resistance rates and estimates that over 100 million
cases per year occur worldwide.

Russell and his colleagues developed the concept that gonococcal
infection seems to inhibit specific adaptive immune responses,
which is, in part, why people can become infected multiple times.
“It turns out that gonococcal infection very cleverly
controls the immune system, inducing responses the bacterium can
fight and suppressing the responses that it cannot fight,” he
said.

In 2013, Russell published a paper describing a potential new
treatment for gonorrhea that modifies the immune response to the
infection. He based the idea on a cancer treatment a colleague had
developed that helps stimulate an immune response against tumors
that normally suppress immunity. The potential treatment not only
reversed the suppression of the immune response that is caused by
the infection, but also established “immune memory,”
providing protection against future reinfections in laboratory
animals.

“This approach, of tweaking the immune system, should work
well against infections of mucosal surfaces – the mouth, the
gastrointestinal system, the respiratory system and the genital
tract, which are where the great majority of infectious diseases
first invade the body,” he says.

He cautions that plenty of research needs to be done to
demonstrate these advantages and that, of course, new and better
antibiotics as well as conventional and novel types of vaccines
must be vigorously pursued.

“But our immune system is extraordinarily capable and
adaptable, and is amenable to exploitation to enhance protective
immunity against a potentially unlimited variety of
pathogens,” he adds. “Because these novel types of
interventions would rely on the ability of the adaptive immune
system to mount a seemingly limitless array of defenses against
pathogens, they should sidestep the problem of antibiotic
resistance.”